Case presentation of 21 yr old male with unresolving pharyngeal ulcers

1. Case presentation of21 yr old male with unresolving pharyngeal ulcers Hoveda Mufti M.D. Memorial Hospital of Rhode Island

2. Chief Complaint: sore throat History of presenting illness: A 21 yr old man of Cape Verde origin presented to ED with complaints of a sore throat. He was empirically treated with Penicillin G IM and Ibuprofen although a rapid strep test was negative. Patient was discharged from the ED, over the next 14 days his symptoms persisted and he developed painful oral and scrotal ulcers. He returned to the ED and was given Ceftriaxone IM and Azithromycin PO and was discharged with a follow up appointment with the Infectious Disease clinic.

3. Patient did not experience relief of his symptoms and developed a painful lower extremity rash which he described as �red bumps� that broke out all over his lower legs. The oral ulcers persisted, he experienced new onset odynophagia, his rash progressed and his overall condition deteriorated. He returned to the ED 19 days after his first presentation and he was admitted for further workup.

4. Review of Systems: Negative for: changes in vision, headaches, sinus pain, shortness of breath, cough, hemoptysis, chest pain, nausea, vomiting, diarrhea, abdominal pain, melena, bleeding per rectum, fever, dysuria, urethral discharge, hematuria, joint pains, calf pain, sick contacts, recent travel. Positive for: Wt loss of 5 lbs over one month, some fatigue in addition to the above complaints.

5. Past medical history: Non significant. No prior hospitalizations. �frequent� sore throat � unable to elaborate further. Not followed by a primary care physician. Surgical: none Allergies: NKDA, no food allergies. Medications: Tylenol prn, Advil prn, ASA prn.

6. Family history: no family members with similar complaints. Social: Fork lift driver. Came to the US in 1992. Drinks 6 pack beer daily, cocaine (snorts) and marijuana use several times a week. Denies IV drug use. 2-3 female sexual partners currently. Denies homosexual encounters. No barrier protection used.

7. Physical Examination: BP: 132/80 P 70/min R 16/min T 97.9 S 98% RA General: No apparent distress. Alert and oriented to place, person and time. Head and neck: Facial acne, shallow ulcers 0.5-1 cm with minimal white exudate around both tonsillar pillars, and 2x2 cm ulcer partially covered by yellow exudate on left posterior pharyngeal wall. No visible bleeding. Enlarged, firm lymph node approximately 8mm in right anterior cervical chain. Anicteric sclera, pupils equal and reactive to light, no nasal mucosa ulcerations.

8. Lungs: clear to auscultation bilaterally. CVS: Regular rate and rhythm of s1 and s2. ABD: soft, non-tender and non-distended. Bowel sounds audible. Liver palpable 1 cm below costal margin. No other masses appreciated. GU: 0.5 cm shallow painful ulcers on scrotum. Regular margins, clean based. No urethral discharge, no inguinal lymphadenopathy or scarring.

9. Extremities: multiple 0.5-1 cm erythematous, minimally raised, purple lesions on lower extremities bilaterally and circumferentially below knees, tender to palpation. 2-4 5 mm pustules w/ yellow discharge on left lower leg. Left ankle minimally swollen and tender to palpation at tibiotalar joint. Rectal: OB negative. No perianal lesions.

14. Laboratory data: Rapid strep test and culture negative. Throat culture for gonorrhea negative Urine/serum tests for Gonorrhea/chlamydia negative STS negative. Upper respiratory culture/Viral throat culture negative . HIV negative Herpes DFA negative PPD negative (< 4mm) Hb 11.5 Hct 34.2 WBC 7.9 N% 67 E% 0.7 Platelets 495 Na 139 K 3.3 CL 100 HCO3 23 BUN 10 Creatinine 0.7

15. AST, ALT, amylase, lipase normal UA: nitrite/ LE negative, WBC/RBC negative, Protein 1+. ESR 109 Chest PA and Lateral: normal with no evidence of hilar adenopathy.

16.  Differential diagnosis of oral ulcers: Herpes Simplex Benign apthous ulcers Inflammatory bowel disease SLE Drugs such as methotrexate Pemphigus vulgaris Hematological disorders such as lymphoma

17. Differential diagnosis of multi-system diseases with such a presentation: SLE Familial mediterranean fever Sarcoidosis Reactive arthritis Multiple sclerosis Behcet�s disease Malignancies Henoch Schonlein purpura

18. Course in hospital: Pt was seen by Infectious disease and Rheumatology and Behcet�s disease was considered the most likely diagnosis. Dermatology obtained biopsies of lower extremities which showed pathology suggestive of Behcet�s disease. This is considered a chronic inflammatory vascular disease of unknown etiology.

19. Pathology of Behcet�s disease Panniculitis with perivascular infiltrates of lymphocytes and neutrophils Leukocytoclastic vasculitis Fibrin thrombi Intraepidermal or subepidermal vesicles and ulcerations Suppurative folliculitis

24. Patient was started on oral Colchicine, Indomethacin and triamcinolone ointment for oral ulcers, which significantly improved his pain. Ophthalmology consulted to rule out complications of this disease, patients ocular exam was normal. He was discharged the next day with instructions to follow up with rheumatology in one week.

25. Discussion: diagnosis Behcet�s disease is a clinical diagnosis. International criteria published in 1990 require the presence of recurrent oral ulcers 3 times in one year plus any two of the following, after exclusion of other systemic diseases: Recurrent genital ulcers eye lesions such as uveitis, retinal vasculitis, or cells in vitreous on slit lamp examination. Skin lesions: erythema nodosum, pseudo-folliculitis papulopustular lesions or acneiform pustules Positive pathergy test: 2mm plus papule developing over 24-48 hrs after oblique insertion of a 20 gauge needle into skin.

26. Pathophysiology Etiology is unknown. Considered a multi-systemic vasculitis. Other theories propose an autoimmune response to an antigen such as infectious agent or environmental agents like heavy metals, in those with genetic predisposition. Acute phase reactants (ESR, CRP) maybe be elevated. Behcet�s disease is a difficult diagnosis to make � oral ulcers and other lesions must be documented by a physician and symptoms may not occur at once and may be separated by a period of several years.

27.  Prevalence More common in Middle Eastern and Far Eastern populations (Japan, Korea, China) but is seen worldwide. Turkey: 80-370/100,000 China: 13-20/100,000 It also varies between men and women indifferent ethnicities for e.g. it�s more common in men in the Middle East, and in women in the Far East (Korea, Japan).

28. Clinical presentation of Behcets A common clinical feature in patients is painful, recurrent muco-cutaneous ulcers. Oral ulcers: Size ranges from a few mm to 2 cm. Grossly and histologically similar to common oral ulcers. Multiple. Often heal spontaneously in 1-3 weeks.

29. Genital ulcers Occur in 75% of patients. Appear similar to oral ulcers. Most frequently scrotal in men, vulvular in women. Epididymitis, salpingitis, urethritis may occur. Cutaneous lesions Acneiform lesions, nodules, erythema nodosum, superficial thrombophlebitis, palpable purpura, pyoderma-gangrenosum. Pathergy test: Less common in North American/European patients. Dermatographism: response to light scratching of skin present in some patients.

30. Ocular disease Less common in North American patients. Uveitis is bilateral, episodic sometimes with no resolution between episodes. Hypopyon: purulent material present in anterior chamber indicating severe anterior uveitis. Posterior uveitis, retinal vasculitis, vascular occlusion, optic neuritis: may progress to blindness if untreated. May require immunosuppressive treatment. Glaucoma, cataracts can occur.

31.  Neurological disease More common in males Occurs in less than 20% of patients Commonest abnormalities are vascular thrombosis and focal parenchymal lesions. Manifestations include: progressive personality change, psychiatric disorders, dementia, aseptic meningitis, encephalitis. Peripheral neuropathy is not common. Arteritis can lead to dissection, aneurysmal dilatation and subarachnoid hemorrhage.

32. Vascular disease Venous involvement occurs more commonly than arterial. Superficial and deep venous thrombosis is common. Many patients have small vessel vasculitis. 30% have large vessel involvement, including stenosis and aneurysms. Pulmonary arterial involvement is characteristic. Hemoptysis made indicate arterio-bronchial fistula. However coronary vascular disease and myocardial infarction are uncommon.

33. Renal disease Usually mild when present - glomerulonephritis. Arthritis is nonerosive, inflammatory oligoarthritis Occurs in 50% of patients Asymmetric and usually does not result in deformities. Commonly affects medium/large joints. Occurs particularly during exacerbations, lasts 1-3 wks.

34. GI disease Symptoms include nausea, diarrhea, abdominal pain. Oral ulcers in Behcet�s are indistinguishable from those found in IBD. When gastrointestinal ulcerations occur they are found in terminal ileum, cecum, ascending colon.

35. Prognosis and clinical course Variable with exacerbations and remissions. Typical presentation is initially with mucocutaneous lesions and subsequently ocular and neurological disease occurring years after diagnosis. Mortality is low and is usually related to pulmonary or CNS hemorrhage or bowel perforation. Most common cause of morbidity is ocular disease which can result in blindness if untreated.

36. Treatment Is based on degree of involvement and individual presentation. Studies of treatment protocols are small. Agents used- mucocutaneous disease Topical steroids Colchicine Dapsone

37. Severe mucocutaneous disease Methotrexate Prednisone Interferon Alpha Thalidomide Systemic disease Prednisone Azathrioprine Cyclophosphamide Anti-TNF drugs

38. Concluding points The diagnosis is difficult particularly in patients with partial symptomatology and also because it relies on clinical criteria. Therefore a high level of suspicion is warranted on part of physicians who may be the first to encounter disease�s initial manifestation. In this patient the series of symptoms fortunately presented in a rapid sequence prompting further investigation. Behcet�s disease was probably first described by Hippocrates in the 5th century and introduced to the modern world by Turkish dermatologist Hulusi Behcet in 1937. The etiology remains ill-defined and the field is open for development of newer and better treatments.